van Meerwijk, Joost P.M. MacDonald, H. Robson <jats:title>Abstract</jats:title> <jats:p>Thymic negative selection renders the developing T-cell repertoire tolerant to self-major histocompatability complex (MHC)/peptide ligands. The major mechanism of induction of self-tolerance is thought to be thymic clonal deletion, ie, the induction of apoptotic cell death in thymocytes expressing a self-reactive T-cell receptor. Consistent with this hypothesis, in mice deficient in thymic clonal deletion mediated by cells of hematopoietic origin, a twofold to threefold increased generation of mature thymocytes has been observed. Here we describe the analysis of the specificity of T lymphocytes developing in the absence of clonal deletion mediated by hematopoietic cells. In vitro, targets expressing syngeneic MHC were readily lysed by activated CD8+ T cells from deletion-deficient mice. However, proliferative responses of T cells from these mice on activation with syngeneic antigen presenting cells were rather poor. In vivo, deletion-deficient T cells were incapable of induction of lethal graft-versus-host disease in syngeneic hosts. These data indicate that in the absence of thymic deletion mediated by hematopoietic cells functional T-cell tolerance can be induced by nonhematopoietic cells in the thymus. Moreover, our results emphasize the redundancy in thymic negative selection mechanisms.</jats:p> https://sonar.ch/global/documents/46413 eng info:eu-repo/semantics/altIdentifier/doi/10.1182/blood.v93.11.3856 info:eu-repo/semantics/altIdentifier/issn/1528-0020 Blood. - American Society of Hematology. - 1999, vol. 93, no. 11, p. 3856-3862 Immunology Cell Biology Biochemistry Hematology In Vivo T-Lymphocyte Tolerance in the Absence of Thymic Clonal Deletion Mediated by Hematopoietic Cells http://purl.org/coar/resource_type/c_6501